Tinnitus - the perception of phantom sounds -is frequently caused by acoustic trauma. This widespread neurological condition affects approximately 40 million people in the U.S. Recent evidence suggests that the auditory brainstem, and in particular, the dorsal cochlear nucleus (DCN), plays a crucial role in the induction of tinnitus. The DCN displays hyperexcitability in tinnitus, hypothesized to result from endogenous compensatory mechanisms in response to acoustic trauma, termed maladaptive plasticity. Multiple mechanisms have been proposed to account for changes to the DCN in tinnitus, but to date, there has been no consensus as to how this brainstem nucleus transitions into a pathological state during this disorder. The DCN has a well-defined synaptic organization and contains multiple inhibitory and excitatory pathways that shape the response properties of this structure to sound. There are a rich variety of synaptic plasticity mechanisms present in the DCN, so factors that influence synaptic plasticity are potential substrates for the chronic hyperexcitability observed in the DCN during tinnitus. The DCN is unique among the auditory brainstem nuclei because it contains high levels of synaptic zinc - a strong regulator of long-term plasticity. Zinc is released from glutamatergic terminals during synaptic transmission, and because it potently inhibits NMDA receptors, it is poised to have a dramatic effect on synaptic signaling. My preliminary data indicate that mice with behavioral evidence of tinnitus have a dramatic reduction of synaptic zinc released from the DCN. This is a novel neurophysiological correlate of tinnitus. I hypothesize that synaptic zinc is critical for the normal functioning of the DCN and tht the loss of zinc is crucial feature of the pathology of the DCN during tinnitus. My preliminary data suggest that reduced synaptic zinc release leads to reduced inhibitory drive in the DCN. This has the potential to change to the balance of excitation and inhibition in the DCN, and be a contributing factor to the hyperexcitability of this structure in tinnitus. I will use newly developed ratiometric fluorescent zinc sensors and chelators in combination with brain slice electrophysiology to examine the role of synaptic zinc in the DCN in normal hearing and in tinnitus. My results will shed new light onto the mechanisms by which the DCN transitions into a state of pathological hyperactivity and potentially offer new strategies for therapeutic interventions for tinnitus.